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ACTIVIN A AND FOLLISTATIN REGULATE PROSTATE BRANCHING MORPHOGENESIS.
Cancilla, Belinda1, Jarred, Renea2, Wang, Hong2, Mellor, Sally2, Cunha, Gerald1, Risbridger, Gail2, 1 2
ABSTRACT- Ventral prostate development occurs by branching morphogenesis and is an androgen dependent process modulated by growth factors. Many growth factors have been implicated in branching morphogenesis including activins (dimers of 
A and B subunits); where activin A was shown to inhibit branching of lung and kidney in vitro. Our aim was to examine the role of activins on prostatic development in vitro, and their localization in vivo. Organ culture of day 0 rat ventral prostates for 6 days with activin A (+/- testosterone) inhibited prostatic branching and growth without increasing apoptosis. The activin-binding protein follistatin increased branching in vitro, suggesting endogenous activins may reduce branching morphogenesis of the prostate. In vivo, inhibin 
subunit was not expressed until puberty, therefore inhibins (which are dimers of inhibin and activin subunits) are not involved in prostatic development. In the developing prostate, activin A was immunolocalized to developing epithelium and mesenchymal aggregates at prostatic ductal tips. Activin B immunoreactivity was weak during development, but was upregulated in prostatic epithelium during puberty. Follistatin mRNA and protein were expressed throughout the prostatic epithelium. The opposing effects of activin and follistatin on ductal branching suggest a role for activin as a negative regulator of prostatic ductal branching morphogenesis.
KEY WORDS: activin, follistatin, prostate, development